Dual role of host cell factors in HIV-1 replication: restriction and enhancement of the viral cycle.

As with other lentiviruses, HIV-1 must be integrated into host cell chromosomes to acquire permanent residence as a provirus. This proviral stage allows HIV-1 to remain silent inside the infected cell, undetectable for the immune response and current antiviral treatment. Once integrated, HIV-1 provirus can subsequently be considered as a host-inducible gene that requires the concerted action of different transcription factors, as well as the RNA polymerase II (RNAPII) and associated transcription machinery, to produce full-length viral mRNA that will be translated into viral proteins. However, efficient viral gene expression represents only the second major step in the viral cycle because an additional process of protein assembly, viral budding, and transmission of fully infective particles is still required to assure viral propagation in the infected host. Accordingly, highly complex mechanisms of viral and cellular measures and countermeasures have been developed during the virus-host co-evolution. On the one hand, viral proteins such as Tat or Nef can modify cellular gene expression1 and change host cell responsiveness to extracellular stimuli2 in order to turn the infected host cells into efficient viral factories. On the other hand, the virus must overcome several cellular antiviral mechanisms that may act at different steps of the viral cycle. The outcome of the match will depend on the imbalance between viral measures and cellular countermeasures. Abstract